Various cancer vaccines based on tumor associated antigens (TAAs) or tumor specific antigens (TSAs) have shown efficacy in preclinical models. However, their therapeutic efficacies have been rather limited in clinical trial settings. Although the reason for clinical inefficacy for these vaccines is not known, the lack of an adjuvant with potent immunostimulatory capacity, ineffective delivery of TAAs/TSAs into professional antigen presenting cells (APCs), and/or the presence of significant immune evasion mechanisms may contribute to this effect. The main objective of this proposal is to develop a novel cancer vaccine for cervical cancer which overcomes these problems. The vaccine, designated ApoVax104-HPV, is based on the use of a proprietary formulation of the costimulatory ligand, 4-1BBL, designed to specifically deliver TAAs/TSAs to APCs. This vaccine formulation also activates APCs for the generation of an effective anti-tumor immune response with therapeutic efficacy. This novel, proprietary molecule consists of 4-1BBL chimeric with core streptavidin and is based on the company's platform technology ProtEx(tm), invented by the co-investigator of this application, Dr. Haval Shirwan. The ApoVax104 technology has been shown in preliminary studies to have potent immunostimulatory activity for T effector cells and inhibitory activity for T regulatory cells that are implicated in tumor growth. A vaccine formulation consisting of ApoVax104 conjugated with the human papillomavirus (HPV)-16 viral oncoprotein E7 will be generated and tested for its efficacy to induce an immune response in C57BL/6 mice. Successful completion of the proposed experiments will be the first step along the critical path for the development of ApoVax104 as the second-generation platform technology for ApoImmune. If ApoVax104-HPV proves effective in these initial proof-of-concept experiments, the Company will apply for a Phase II SBIR grant to further develop ApoVax104-HPV into a lead commercial product to test in a Phase I clinical trial. In addition, ApoVax104 vaccines may not only protect against cancer but also against infectious diseases, leading to the development of an entire line of ApoVax104-based vaccines with significant potential in the millions of dollars. Immune system-based treatment of cancer represents an alternative therapeutic approach to classic chemotherapy and radiation treatment, and promises to yield a more definitive solution based on a true molecular approach to cancer. ApoImmune's novel immune system-based therapy, ApoVax104 vaccine, is a new, innovative approach to treating cancer and malignant neoplastic diseases. [unreadable] [unreadable]